Dynamic PET Imaging of Elesclomol-Facilitated Copper Delivery in Ischemic Stroke Rats

Copper is an essential trace element that is required at optimal levels to support physiological functions in the cerebrovascular system. Copper deficiency reduces vascular elasticity, potentially worsening the ischemic stroke. Epidemiological evidence has linked higher copper intake with reduced stroke risk. This study aimed to investigate Elesclomol (ES) as a vector for delivering copper to the brain in models of ischemic stroke. 64Cu-ES showed excellent serum stability in vitro. PET/CT imaging revealed that 64Cu-ES exhibited longer brain retention compared to 64Cu-ATSM, likely due to its higher lipophilicity. Ex vivo biodistribution results were consistent with the imaging data. In normal SD rats, 64Cu-ES showed the highest uptake in the cingulate cortex, followed by the striatum, cerebral cortex, hippocampus, thalamus, and pons, with the lowest levels in the cerebellum and amygdala. In ischemic SD rats, there was no significant difference in the 64Cu-ES uptake between the ischemic region and the contralateral side up to 24 h post-administration. These results provide direct evidence that ES can facilitate delivery of copper to the brain, supporting its potential as a therapeutic candidate for copper supplementation in ischemic stroke patients.